ACCELERATING the CURE WINTER 2006 NEWSLETTER GENE THERAPY: THE NEXT GENERATION NEWS FROM THE $4.2 MILLION LEAPS AWARD WILL JUMP-START PRESIDENT AND CEO DEVELOPMENT OF REGULATABLE GENE THERAPY The thread that runs through all of the he Michael J. Fox Foundation for The project will begin with a focus on two Foundation’s work is Parkinson’s Research (MJFF) has com- genes. One produces small molecule GDNF, the question we ask mitted $4.2 million to a team led by a potent neurotrophic factor; the other pro- T about every prospec- RheoGene Inc. to develop what could be the duces large molecule AADC, an enzyme tive research invest- next generation of gene therapy: a delivery involved in dopamine synthesis. Both genes may ment: What is the system that would provide clinicians a “switch” have therapeutic merit, and different technolo- potential of this tool, to control a gene implanted in a patient’s brain. gies may be required to regulate each. By work- study or trial to shorten patients’ wait for In collaboration with several academic institu- ing on both, the research team can widen the improved Parkinson’s treatments and, ultimately, tions, RheoGene will develop, optimize and test variety of genes to which the regulation switch a cure? Our driving goal is to propel scientific its “RheoSwitch® Therapeutic System” (RTS) they develop could ultimately be applicable. Like discoveries beyond academia, through the technology through Phase I clinical trials within all LEAPS awards, the project hinges on specific translational gap where promising ideas too often four years. While Parkinson’s disease is the first milestones that will determine whether work languish, and into the clinic for translation into application, the work will have broad applicabil- on one or both of the genes ultimately goes forward. meaningful therapies and interventions. ity to the safety and efficacy of gene therapies for many other diseases as well, and for their The RheoGene award is also a reflection of the This issue highlights some major recent Foundation’s increasing interest in neurotrophic accelerated advancement into the clinic. expressions of the Foundation’s commitment factor research, to which MJFF’s funding com- to translational research. They include a LEAPS “This project has potential to revolutionize the mitment to date totals about $8.5 million. award that could spawn the next generation clinical application of gene therapy,” said Neurotrophic factors (also known as trophic or of gene therapy, a validation study of genes Deborah W. Brooks, MJFF president and CEO. growth factors) have long been considered one implicated in PD, and a project that builds on “It is a natural fit with the Foundation’s commit- of the most promising avenues of Parkinson’s a promising Alzheimer’s therapy to drive a ment to drive innovative technology that will research, as they promote survival and improve potential new treatment for Parkinson’s. have a significant impact on patients’ lives.” function of neurons. (For more information on trophic factors, see box, page 2.) You’ll also see, as a special insert, our 2005 Gene therapy has been touted for years as Progress Report. As we enter our sixth year, a prospective cure-all for a wide range of health “We are very excited that the Fox Foundation we assess our progress and accomplishments ailments. But its development as a widespread has recognized RheoGene’s ability to create to date, including driving the first dopaminer- therapeutic technique has been hampered by leading-edge technology,” said Thomas Tillett, gic human stem cell line and the first large- the lack of any way to time or finely adjust doses CEO of RheoGene. “This grant will enable us to scale genetic map of Parkinson’s — tools with or to “turn off” a gene once it has begun continue to build on our successes with RTS potential to transform the way Parkinson’s is expressing a protein in the brain. The to date in creating innovative solutions that pro- diagnosed and treated. RheoGene-led team will work to establish RTS vide safer and more effective gene therapies.” as a safe and effective means to regulate both We take pride in what we’ve achieved so far, but the level (dose) and timing of gene expression The award is made under the Foundation’s we won’t rest until we reach our goal: a world using an orally administered activator drug, or LEAPS (Linked Efforts to Accelerate Parkinson’s where Parkinson’s disease is only a memory. “on switch.” The advent of RTS would furnish an Solutions) initiative. LEAPS are multi-year, multi- unprecedented safety mechanism by allowing million, multi-disciplinary projects to address Warm regards, gene expression to be completely shut off in the questions that will have significant practical event of adverse side effects, simply through impact on the understanding and treatment of withdrawal of the activator drug. Parkinson’s disease. Deborah W. Brooks President and CEO See Page 4 for Members of the RheoGene-led LEAPS Team PAGE 2 FOUNDATION SUPPORTS CEREGENE INC. PHASE 1 CLINICAL TRIAL IN THIS ISSUE PAGE 3 MJFF-FUNDED RESEARCHERS PUBLISH FIRST WHOLE-GENOME MAP OF PARKINSON’S PAGE 4 $3.1 MILLION FOR POTENTIAL NEW THERAPY TO STOP PD PROGRESSION Research News BOARD OF DIRECTORS FOUNDATION SUPPORTS CEREGENE, INC. Michael J. Fox PHASE I GENE THERAPY CLINICAL TRIAL Holly S. Andersen, MD Eva Andersson-Dubin, MD he Michael J. Fox Foundation has com- for more routine procedures such as blood tests). Mitchell Blutt, MD Barry Cohen mitted $740,000 over three years to Assuming successful results, measurements from Donny Deutsch T Ceregene, Inc., a San Diego-based the Phase I study will lead to more efficient plan- David Einhorn biotechnology company focused on the develop- ning of a larger Phase II study that will gather Karen Finerman ment of gene therapies for neurodegenerative more detailed data on both safety and efficacy. Nelle Fortenberry Al Glickman disorders. The grant, announced in November, David Golub will help fund Ceregene’s Phase I clinical study of “Extensive studies in animal models, including the John Griffin CERE-120, a new gene therapy product that has most widely accepted models of Parkinson’s Rev. Msgr. Thomas J. Hartman shown potential in pre-clinical testing to slow or disease, have consistently demonstrated that Jeffrey Katzenberg Kathleen Kennedy stop the progression of Parkinson’s disease by CERE-120 is safe and well tolerated in animals Morton Kondracke using a viral vector to deliver neurturin, a potent even at doses hundreds of times higher than the Edwin Levy nervous system growth factor. equivalent doses being tested in humans. These Nora McAniff studies also demonstrate that CERE-120 may be Kenneth Olden, PhD Douglas I. Ostrover “The Phase I trial of CERE-120 brings several able to improve symptoms as well as slow the Tracy Pollan Foundation priorities to bear,” said Deborah W. progression of Parkinson’s disease,” said Raymond George Prescott Brooks, MJFF president and CEO. “These include T. Bartus, PhD, Ceregene’s COO and principal Michael Price Lily Safra investigating the neurorestorative properties of investigator on the grant. Curtis Schenker neurotrophic factors [see box], advancing transla- Donna Shalala, PhD tional research, and shortening the time it takes The Foundation funding supplements Ceregene’s Daniel Spitzer, MD to turn basic research advances into meaningful own multi-million dollar investment in the study, Fred Weiss therapies for patients.” which is under way at the University of California, President and CEO San Francisco Medical Center and Rush Deborah W. Brooks While the primary goal of any Phase I clinical University Medical Center in Chicago. study is to demonstrate safety, Ceregene will also SCIENTIFIC measure the efficacy of CERE-120 through brain “We’re pleased to have Fox Foundation support ADVISORY BOARD imaging studies and standardized Parkinson’s to optimize our clinical tests of CERE-120,” said tests. MJFF support will significantly enhance the Jeffrey M. Ostrove, PhD, president and CEO of Alberto Ascherio, MD, PhD speed and depth of this data collection, allowing Ceregene. “This funding will allow us to gather, Erwan Bezard, PhD Anders Bjorklund, MD, PhD* for more regular testing of a wider range of neu- in the shortest time possible, the data needed to Susan Bressman, MD rological functions than would otherwise be pos- know if we are on to a safe therapy that might David J. Brooks, MD sible. Each patient will undergo a PET scan and a slow or stop the progression of the disease — Robert E. Burke, MD Marie-Francoise Chesselet, MD, PhD* full battery of neurological tests every three something no treatment on today’s market can do.” P. Jeffrey Conn, PhD months (in addition to regular visits to the clinic Continued on Page 8 Mark Cookson, PhD David Eidleberg, MD Matt Farrer, PhD Chip Gerfen, PhD Fred Goldberg, PhD Why trophic factors? Tim Greenamyre, MD, PhD* Oleh Hornyklewicz, MD “Neurotrophic factors work in the brain the required for normal bodily movement and that Ole Isacson, MD (Dr. MD Sci) way fertilizer works in a field,” says Todd degenerate in people with Parkinson’s. Joseph Jankovic, MD Sherer, PhD, MJFF associate director of Gene Johnson, PhD* research programs. “As the fertilizer helps Other MJFF investments in neurotrophic fac- Jennifer Johnston, PhD* Jeffrey H. Kordower, PhD crops to thrive, neurotrophic factors promote tors to date include two current LEAPS (Linked J. William Langston, MD* survival and improve function of neurons.” Also Efforts to Accelerate Parkinson’s Solutions) Olle Lindvall, MD, PhD known as trophic or growth factors, these projects and two Community Fast Track 2004 Andres Lozano, MD, PhD* molecules have long been considered one of Kenneth Marek, MD projects.